Romidepsin
A bacterial depsipeptide HDAC inhibitor approved for cutaneous T-cell lymphoma
Romidepsin is a two-ringed depsipeptide that blocks histone deacetylase enzymes. Approved as Istodax in 2009 for cutaneous T-cell lymphoma, it also held an accelerated approval for peripheral T-cell lymphoma from 2011 until that indication was withdrawn in 2021.
Manufacturer's recommended dosing (FDA label): 14 mg/m², Days 1, 8 and 15 of a 28-day cycle, Intravenous, over 4 hours Details ↓
Recommended Dosing
Manufacturer's recommended dosing (FDA label)
From the prescribing information. Other doses studied, if any, are in the full dosing data below.
What is it?
Romidepsin, first known as FK228 or depsipeptide, is a two-ringed peptide in which one link is an ester rather than an amide bond, the definition of a depsipeptide. It blocks histone deacetylases, enzymes that remove acetyl groups from histones and so change which genes are read, and in cancer cell lines that halts division and triggers cell death. It is a prescription cancer drug given only by intravenous infusion over four hours, never a research peptide for personal use.
Its approval rests on two single-arm trials in cutaneous T-cell lymphoma, the group of lymphomas that includes mycosis fungoides and Sézary syndrome. In an international pivotal trial of 96 patients, 34% responded, responses lasted a median 15 months, and 43% reported meaningful relief of itching. A US National Cancer Institute trial in 71 patients found the same 34% response rate. The FDA approved Istodax for CTCL after at least one systemic therapy in November 2009.
Its second indication did not last. In 2011 it received accelerated approval for peripheral T-cell lymphoma, based on a pivotal trial with a 25% response rate, 15% complete, some lasting years. Accelerated approval depends on later confirmation of benefit. The Ro-CHOP phase 3 trial in 421 untreated patients then found that adding romidepsin to standard chemotherapy did not improve progression-free or overall survival and caused more severe low blood counts. The PTCL indication was withdrawn on July 30, 2021, and the current US label lists CTCL only. The EU had refused it for PTCL in 2013.
Side effects are those of a cytotoxic drug: nausea, fatigue, infections, low platelets and white counts, and electrocardiogram changes. In an intensive cardiac study, more than half of post-dose ECGs showed T-wave or ST changes and the corrected QT interval rose by about 14 milliseconds on average, without heart muscle damage; the label asks for normal potassium and magnesium before each dose. Infections, including reactivation of hepatitis B and Epstein-Barr virus, have been fatal.
Romidepsin has also been tested at lower doses as a way to wake dormant HIV in people on antiretroviral therapy; in a six-person study it made the virus detectable in the blood of five without blunting T-cell responses. That is research, not an approved use.
Mechanism of Action
Romidepsin is a histone deacetylase inhibitor (Istodax label 12.1).
HDAC inhibition
Blocks histone deacetylases, so acetylated histones accumulate and gene expression changes (label 12.1).
Published Research
The studies behind romidepsin, read from their PubMed abstracts: the CTCL trials behind the approval, the PTCL trials behind the withdrawn indication, and safety and pharmacology work.
Pivotal trial in refractory CTCL
In 96 patients with stage IB to IVA CTCL after at least one systemic therapy, romidepsin 14 mg/m² on days 1, 8 and 15 every 28 days produced responses in 34% (six complete), lasting a median 15 months; 43% had meaningful relief of itching, and side effects were mostly mild stomach upset and tiredness.
NCI phase 2 trial in CTCL
In 71 patients with a median of four prior treatments, 87% with advanced disease, the response rate was 34% (4 complete, 20 partial) with a median duration of 13.7 months; toxicity included nausea, vomiting, fatigue and transient drops in platelets and white cells.
PTCL pivotal trial, updated
In 130 patients with relapsed or refractory peripheral T-cell lymphoma, 25% responded and 15% had complete or unconfirmed complete responses; responses lasted a median 28 months, and some complete responses were ongoing at 48 months.
NCI phase 2 trial in PTCL
In 45 evaluable patients with relapsed peripheral T-cell lymphoma after a median of three prior treatments, 38% responded (8 complete, 9 partial), with a median response duration of 8.9 months, including six responses after stem-cell transplant.
Ro-CHOP: no gain added to CHOP
In 421 untreated PTCL patients, romidepsin 12 mg/m² on days 1 and 8 with CHOP gave a median progression-free survival of 12.0 months against 10.2 with CHOP alone (not significant), with more severe low platelets (50% against 10%) and neutrophils (49% against 33%).
Ro-CHOP: final analysis
After a median six years, progression-free survival (hazard ratio 0.79) and overall survival (62.2 against 43.8 months, hazard ratio 0.88) were still not significantly better with romidepsin; one subgroup, follicular helper T-cell lymphoma, did better in an exploratory analysis.
Real-life results in Israel
In 53 patients treated outside trials, response was 25% in CTCL and 33% in PTCL; PTCL patients had a median survival of 7.1 months, infections affected 34%, and responders lived longest.
Heart monitoring on treatment
In 42 patients with 2,051 ECGs, T-wave flattening or ST depression appeared on more than half of post-dose tracings without troponin rise or loss of heart pumping function; the corrected QT interval rose by a mean 14.4 ms, and electrolyte replacement was added.
Population pharmacokinetics
In 98 patients given 14 or 18 mg/m² over four hours, romidepsin followed a two-compartment model with a clearance of 15.9 L/h and 37% between-patient variability; variants in CYP3A4, CYP3A5 and SLCO1B3 did not change exposure.
Waking latent HIV
In six people with HIV on antiretroviral therapy, three weekly infusions of romidepsin 5 mg/m² raised HIV transcription and made plasma virus measurable in five, without reducing HIV-specific T cells; side effects were grade 1 to 2.
Dosing Data
Istodax is reconstituted with its supplied diluent, diluted in saline and infused over four hours. The label's dose and adjustments are below.
Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
What a Buyer Needs to Know
What is sold, how it is mixed, stored and taken, and what is known about its safety, quality and legal status. Each part names its source. Where we have none, it says unknown.
What is sold
The approved product, as its label describes it:
- Istodax (romidepsin kit): For injection: 10 mg of romidepsin as a lyophilized powder in single-dose vial for reconstitution. Forms the label lists: single-dose vials.
Source: Istodax (romidepsin kit) label, section 3 (DailyMed version 22, effective January 31, 2023).
Mixing a vial: a worked example
Nothing to mix at home, and no syringe units to work out: Romidepsin is prepared and given by clinical staff, by a cancer team in an infusion centre or hospital.
Its US label gives it as a four-hour infusion into a vein on set days of a 28-day cycle, and calls it a hazardous drug for those preparing it.
Source: Istodax (romidepsin kit) label, section 2 (DailyMed version 22, effective January 31, 2023).
Storage before and after mixing
Before mixing or first use: “The carton must be stored at 20° to 25°C, excursions permitted between 15° to 30°C. (See USP Controlled Room Temperature.) ISTODAX is a hazardous drug.”
After mixing or first use: “The diluted solution is compatible with polyvinyl chloride (PVC), ethylene vinyl acetate (EVA), polyethylene (PE) infusion bags as well as glass bottles, and is chemically stable for up to 24 hours when stored at room temperature.”
Source: Istodax (romidepsin kit) label, sections 16 and 2 (DailyMed version 22, effective January 31, 2023).
How it is taken
As the approved label gives it: Intravenous, over 4 hours (Days 1, 8 and 15 of a 28-day cycle; Label: cutaneous T-cell lymphoma).
Source: Manufacturer's recommended dosing (FDA label): the route and frequency of each row in Dosing Data below.
What to expect, and when
How long it stays in the body: a half-life of about 3 hours. After about five half-lives almost none is left.
How long the doses were given: Label: cutaneous T-cell lymphoma: Repeat every 28 days while the patient benefits and tolerates it; Label: after grade 3 or 4 toxicity: Stop if grade 3 or 4 toxicity recurs after the reduction; Label: moderate or severe liver impairment: Starting dose; monitor more often.
When effects appear: unknown; no source on this page gives a time to effect for Romidepsin. Results reported in the studies are under Published Research.
Source: half-life: Istodax prescribing information, section 12.3 (DailyMed set 03b39d40, version 22, effective January 31, 2023); Manufacturer's recommended dosing (FDA label), the duration of each row in Dosing Data below.
Side effects, and when to stop or get help
From the Side Effects section: Nausea, vomiting, fatigue and loss of appetite; Low platelets and white cells, severe when combined with CHOP; ECG T-wave and ST changes and a small rise in QT interval; Infections, in about a third of patients in routine practice. Full list and cautions ↓
When to stop or get help: unknown; the label's warnings summary we read gives no rule for stopping Romidepsin. Treat a severe or unexpected reaction as a reason to stop and see a doctor.
Source: the Side Effects section below (“From the studies above”).
Interactions
- warfarin or coumarin derivatives: PT prolongation and INR elevation were seen in a patient on both; monitor PT and INR more often
- strong CYP3A4 inhibitors: raise romidepsin exposure; monitor for toxicity
- rifampin and strong CYP3A4 inducers: avoid the combination
Every peptide's record, with its source: the interaction matrix.
Source: Istodax (romidepsin) for injection, US prescribing information, section 7. DailyMed set 03b39d40, version 22, effective January 31, 2023, read October 28, 2026.
Checking what you bought
Unknown: no published independent test of Romidepsin products is in our lab-results database yet, so how products sold under this name measure up is not known.
To read a certificate of analysis, paste it into the COA decoder; it checks the measured mass against Romidepsin's expected mass, 540.7 Da, from this entry's molecular data. Trust & Verification explains what independent testing can and cannot show.
Legal status
US: FDA Approved (FDA-approved as Istodax (NDA 022393) on November 5, 2009 for cutaneous T-cell lymphoma (CTCL) in adults who have received at least one prior systemic therapy, its only current US indication (US prescribing information, DailyMed set 03b39d40, version 22)). Sport: Not on the 2026 List.
Country by country ↓ · Regulatory tracker
Source: this entry's approval status and the WADA Prohibited List, as in Legal Status below.
Side Effects & Contraindications
Reported Side Effects
From the studies above.
Contraindications & Cautions
Warnings from the Istodax label (DailyMed set 03b39d40, version 22, effective January 31, 2023). It has no boxed warning and no contraindications.
Legal Status
Romidepsin is approved in the US for cutaneous T-cell lymphoma only.
Frequently Asked Questions
?What is romidepsin?
A bicyclic depsipeptide that inhibits histone deacetylase enzymes. It is sold as Istodax, an intravenous cancer drug.
?What is it approved for?
In the US, cutaneous T-cell lymphoma in adults who have had at least one systemic therapy. That is its only current indication.
?Was it approved for peripheral T-cell lymphoma?
Yes, by accelerated approval in 2011. The later Ro-CHOP phase 3 trial found no survival benefit from adding it to chemotherapy, and the FDA lists the PTCL indication as withdrawn on July 30, 2021.
?How well does it work in CTCL?
About a third of patients with treatment-resistant CTCL responded in its two main trials, with responses lasting more than a year on average and itching often improving.
?Does it affect the heart?
It commonly causes ECG changes and a small rise in QT interval. A monitoring study found no damage to heart muscle, but the label asks for normal potassium and magnesium and extra monitoring in people with heart disease.
?Is it used for HIV?
It has been studied as a way to reactivate dormant HIV in people on treatment. That is experimental and not an approved use.
References
- [fda-pi] Istodax (romidepsin) for injection, US prescribing information, sections 1, 2, 7, 11 and 12.3 (Celgene; DailyMed set 03b39d40, version 22, effective January 31, 2023; read October 28, 2026).
- [other] PubChem CID 5352062, Romidepsin: formula C24H36N4O6S2, molecular weight 540.7. Read October 28, 2026. https://pubchem.ncbi.nlm.nih.gov/compound/5352062
- [clinical-trial] Bachy E, et al. "Romidepsin Plus CHOP Versus CHOP in Patients With Previously Untreated Peripheral T-Cell Lymphoma: Results of the Ro-CHOP Phase III Study (Conducted by LYSA)." J Clin Oncol, 2022;40(3):242-251. PMID: 34843406.
- [review] Pojani E, et al. "Romidepsin (FK228), A Histone Deacetylase Inhibitor and its Analogues in Cancer Chemotherapy." Curr Med Chem, 2021;28(7):1290-1303. PMID: 32013816.
- [other] European Medicines Agency, medicines list (JSON report, downloaded October 28, 2026): Istodax (romidepsin), orphan medicine for peripheral T-cell lymphoma: marketing authorisation refused, refusal dated February 12, 2013.
- [fda] US FDA, Drugs@FDA (openFDA): ISTODAX (romidepsin), NDA 022393; original approval November 5, 2009; marketing status Prescription. Read October 28, 2026.
- [fda] US FDA, Withdrawn | Cancer Accelerated Approvals: Istodax (romidepsin), peripheral T-cell lymphoma in patients who have received at least one prior therapy; accelerated approval June 16, 2011, withdrawn July 30, 2021 (page content current as of October 5, 2026; read October 28, 2026).
- [clinical-trial] Whittaker SJ, et al. "Final results from a multicenter, international, pivotal study of romidepsin in refractory cutaneous T-cell lymphoma." J Clin Oncol, 2010;28(29):4485-91. PMID: 20697094.
- [clinical-trial] Piekarz RL, et al. "Phase II multi-institutional trial of the histone deacetylase inhibitor romidepsin as monotherapy for patients with cutaneous T-cell lymphoma." J Clin Oncol, 2009;27(32):5410-7. PMID: 19826128.
- [clinical-trial] Coiffier B, et al. "Romidepsin for the treatment of relapsed/refractory peripheral T-cell lymphoma: pivotal study update demonstrates durable responses." J Hematol Oncol, 2014;7:11. PMID: 24456586.
- [clinical-trial] Piekarz RL, et al. "Phase 2 trial of romidepsin in patients with peripheral T-cell lymphoma." Blood, 2011;117(22):5827-34. PMID: 21355097.
- [clinical-trial] Camus V, et al. "Romidepsin Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone Versus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone in Patients With Previously Untreated Peripheral T-Cell Lymphoma: Final Analysis of the Ro-CHOP Trial." J Clin Oncol, 2024;42(14):1612-1618. PMID: 38364196.
- [pubmed] Shimony S, et al. "Romidepsin treatment for relapsed or refractory peripheral and cutaneous T-cell lymphoma: Real-life data from a national multicenter observational study." Hematol Oncol, 2019;37(5):569-577. PMID: 31674027.
- [clinical-trial] Piekarz RL, et al. "Cardiac studies in patients treated with depsipeptide, FK228, in a phase II trial for T-cell lymphoma." Clin Cancer Res, 2006;12(12):3762-73. PMID: 16778104.
- [pubmed] Woo S, et al. "Population pharmacokinetics of romidepsin in patients with cutaneous T-cell lymphoma and relapsed peripheral T-cell lymphoma." Clin Cancer Res, 2009;15(4):1496-503. PMID: 19228751.
- [clinical-trial] Søgaard OS, et al. "The Depsipeptide Romidepsin Reverses HIV-1 Latency In Vivo." PLoS Pathog, 2015;11(9):e1005142. PMID: 26379282.
Sources & Citations
Studies were read from their PubMed abstracts; the label from DailyMed (Istodax, set 03b39d40, version 22, effective January 31, 2023), read October 28, 2026; approval and withdrawal records from Drugs@FDA, the FDA's list of withdrawn cancer accelerated approvals and the EMA.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.